1. Field of the Invention
This invention pertains to the field of treating and preventing signs and symptoms of aging.
2. Background
Therapeutic products comprising metallic moieties have been used for many years for a variety of skin diseases. These medications have continued to be used to treat one or several skin diseases. For example, zinc pyrithione (zinc pyridine-2-thiol-1-oxide) is a therapeutic molecule that is used as the active ingredient in the most widely Distributed commercially available medicated shampoos for treatment of dandruff and seborrheic dermatitis. In the past year, this compound has been introduced by two companies in a topical leave-on product to treat scalp psoriasis. Zinc pyrithione has multiple mechanisms of action including antiproliferative, keratolytic, astringent, antibacterial and anti-yeast properties. Zinc undecylenate has also been used as an antifungal agent. Zinc oxide has also had a long history as a sunblock and skin protectant especially for the diaper area. Zinc lactate 0.15% is one component of a prescription product which also comprises erythromicin 2% in a topical therapy for acne vulgaris.
U.S. Pat. No. 4,307,089 discusses a formulation that contains zinc pyrithione and/or its tautomeric form combined with undecylenic acid and the use of the formulation to treat dandruff. U.S. Pat. No. 5,284,649 discusses the use of heavy metal salts of hydroxypyridine thiones and their tautomeric forms, including zinc, zirconium, cadmium, tin, magnesium, sodium, calcium, aluminum and potassium pyrithione, as human deodorants.
Zinc is an essential mineral for animal cell growth and regeneration due to its integral structural role in certain enzymes especially proteases including carboxypeptidase A. Furthermore, the deoxyribonucleic acid (DNA) contains zinc finger binding domains utilized in transcription thus regulating gene activity. This element also functions as an enzyme activator, a coenzyme, and an antioxidant. Zinc and other bivalent ions including cobalt, copper, nickel, and manganese inhibit the binding of triiodothyronine lo its nuclear receptor. Zinc, selenium, vanadium, and chromium all have documented insulin mimetic activity.
Selenium is a known antioxidant utilized as an immune modulator in naturpathic and lay medicine. Its major mechanism of action is via covalent binding to the key detoxification/antioxidant enzyme glutathione peroxidase. Multiple selenium sulfide shampoos have been on the prescription and over-the-counter markets for years to treat dandruff and seborrheic dermatitis. The difference between the two markets is that the prescription product has a much higher concentration of the selenium sulfide. These products are generally considered to be more effective than zinc pyrithione because of documented superior anti-microbial activity.
Multiple enzymes are known to require metallic ions as cofactors or are needed as catalysts. Several other of metals currently are or have been in the past used a human disease medicines. Arsenic was a major topical treatment for psoriasis prior to the advent of corticosteriods. Gallium formulations injected intravenously are used in human medical diagonstic tests. Copper and silver salts are the active ingredients ir topical products for cleansing and deodorizing stomas and burns. Strontium has been reported to treat stinging/burning due to neurogenic inflammation but is associated with bone deposition and marrow suppression.
Use of these metallic compounds as therapeutic compounds would be expected to have serious drawbacks because several, including nickel, chromium, and cobalt, are potent contact sensitizers of the skin and mucous membranes. Iron is a potent oxidant inducing cell damage. Bromine often induces a characteristic dermatosis known as bromoderma. High calcium levels in the stratum corneum inhibit normal barrier formation and desquamation.
Chronologically aged (intrinsic aging) mucocutaneous surfaces show a slight atrophy of the epidermis with straightening of the rete pegs thus weakening the dermal/epidermal junction measured by a decrease in the threshold for suction bullae. There is a moderate decrease in the number of Langerhans cells. Dryness of the skin is a common phenomenon. In the dermis there is lower cellularity and a decrease in elastic fibers and thus in skin elasticity. Capillaries are also fragile as evidenced by bruisability. Collagen metabolism is slower, and there is a progressive lowering in concentration of glycosaminoglycans. Wrinkling occurs, but it tends to be in the form of fine wrinkles that disappear temporarily with stretching. There is a decreased ability to mount inflammatory response and an increase in the time of healing after injury.
Photoaging induces deep wrinkles not erased by stretching, pigmentary alterations with areas of hyper- and hypopigmentation (actinic lentigines and leukodermas), and a variety of benign, premalignant, and malignant neoplasms. The dermis shows evidence of chronic inflammation with increased cellularity and enlarged fibroblasts. Elastotic degeneration occurs in which parts of the upper dermis is occupied by a basophilic fibrous material separating the dermis from the epidermis. This "grenz" zone is interpreted as a repair area. Glycosaminoglycan concentrations is increased, while elastin concentration is increased and arranged in atypical clumps. Collagen fibers are fragmented.
A need exists for methods and compositions that are effective in preventing and/or reversing signs and symptoms of aging. The present invention fulfills these and other needs.